Rehabilitation with implant-supported overdentures in preteens patients with ectodermal dysplasia: A cohort study.

INTRODUCTION: Hypohidrotic ectodermal dysplasia (HED) patients suffering of oligo-anodontia require early dental treatment to improve oral functions and reduce social impairment. The aim of this study was to evaluate the skeletal growth, implant and prosthetic survival rate, success, and complications after the rehabilitation with a maxillary denture and an implant-supported overdenture provided by a sliding bar in case of severe hypodontia/anodontia related to HED. MATERIALS AND METHODS: This retrospective cohort study began in 2009. Nine patients over 7 years old with HED and associated oligo-anodontia who presented at the University of Bologna for dental treatment were included in the study. They were first treated with conventional dentures and then with a maxillary denture and an implant-supported overdenture with a sliding bar connected to two implants placed in the anterior mandible. The subjects treated were followed for 3-12 years. In each case, orthopanoramic and lateral cephalometric radiographic exam were taken before implant placement and annually after prosthetic load. Vertical and transverse dimensions of the mandible in the symphysis area at implant sites were taken on the lateral cephalometric radiography at the time of implant placement and after 5 years from the prosthetic loading to assess the presence or absence of an anterior mandibular growth. Biologic and mechanical complications were also recorded at every visit. RESULTS: A mandibular vertical growth under the implant apex, at the implant neck, and a sagittal growth of the symphysis after 5 years from the prosthetic loading were observed and measured. Implant and prosthetic success and survival rates were 100% after 8.1 years (mean) follow-up period. No complications were reported except in one patient, where the repositioning of a retentive cap on the counter bar in the superstructure was necessary after 3 years from the prosthetic loading. CONCLUSIONS: The present study suggests that the growth of the mandible near implant sites continues even after their positioning. Implants can be successfully placed and provide support for prosthetic rehabilitation in preteens patients with HED.

PSA flare with abiraterone in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome. PATIENTS AND METHODS: We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes. RESULTS: Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively. CONCLUSION: PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon.

Gemcitabine and paclitaxel combination as second-line chemotherapy in patients with small-cell lung cancer: a phase II study.

BACKGROUND: Although small-cell lung cancer is a chemosensitive malignancy, most patients rapidly relapse. Results of second-line treatment are generally poor. We conducted a phase II study to evaluate the activity and toxicity of a combination of gemcitabine and paclitaxel as second-line chemotherapy. PATIENTS AND METHODS: Eligible patients were refractory or relapsed small-cell lung cancer, with an Eastern Cooperative Oncology Group performance status of 0-2 and measurable disease. Paclitaxel was administered at 135 mg/m(2) days 1 and 8 immediately followed by gemcitabine at 1000 mg/m(2) every 3 weeks up to 6 courses. Restaging of disease was scheduled every 3 courses. RESULTS: Forty-one patients were enrolled. The median age was 65 years. Nineteen patients were considered refractory (progressive disease during or within 90 days from completion of first-line treatment), whereas 22 patients were chemotherapy sensitive. A total of 135 courses was administered (range, 1-6; median, 3). Nine patients achieved a partial remission (partial response, 22%), and 10 patients had stable disease (24%), with a disease control rate (partial response + stable disease) of 46%: in 12 (55%) of 22 patients who were sensitive and in 7 (37%) of 19 patients with refractory disease, respectively. All partial responses but one were observed in the sensitive group. The median duration of response was 5 months. The most-frequent severe toxicities were neutropenia grade 3-4 and neurologic grade 3 in 24% and 7% of delivered courses, respectively. CONCLUSIONS: The combination of gemcitabine and paclitaxel investigated in our study achieved a high disease control rate, but the schedule we adopted appeared to be quite toxic.

Oral rehabilitation of children with ectodermal dysplasia.

The aim of this study was to describe the clinical treatment of young patients, affected by ectodermal dysplasia (ED), and to possibly establish clinical guidelines. The study design was case series. ED syndromes (EDs) are a heterogeneous group of inherited diseases characterised by abnormal development of tissues of ectodermal origin. The most common form of EDs is X linked hypohidrotic ED (HED). Characteristic triad of HED is oligo-anodontia, hypotricosis, hypo-anhydrosis. Oligo-anodontia is one of the most severe impairment, since it affects chewing, swallowing, speech, esthetics and social relation. Early prosthetic rehabilitation (at 2-3 years of age), with partial or complete dentures, is essential to improve oral function and reduce the social impairment.

Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer.

AIMS AND BACKGROUND: Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy. METHODS: Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. RESULTS: Median patient age was 69 years (range, 52-83) and median baseline PSA concentration was 120 ng/mL (range, 5.35-4350). Sixteen (29.6%) patients had measurable lesions. Objective or PSA responses (>50% reduction) were observed in 8 (14.8%) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1-2) and infrequent, with grade 3-4 neutropenia in 12.9% of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7%) and fatigue and stomatitis in 1 case (1.9%). No drug-related serious adverse events were reported. CONCLUSIONS: Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.

Activity of different anthracycline formulations in hormone-refractory prostate cancer cell lines: role of Golgi apparatus.

The efficacy of therapy for hormone-refractory prostate cancer (HRPC) is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of doxorubicin (DX), pegylated liposomal DX (PLDX), and non-pegylated liposomal DX (NPLDX) in DU145 and taxane-resistant DU145-R HRPC cell lines. Drug activity and incorporation, apoptosis, and expression of cell death-related markers were evaluated by SRB test, cytofluorimetric assays, and Western blot, respectively. Among the different DX formulations, NPLDX showed the highest cytotoxic activity in both cell lines, with more than 50% of apoptotic cells at only 1/10 of the plasma peak concentration after 72 h exposure. Anthracyclines, in particular NPLDX, were highly concentrated in the Golgi apparatus. Moreover, a significant increase was observed in the expression of CD95 receptor, GD3 ganglioside and, caspase-2 and -8 active forms in both cell lines followed by caspase-3 activation and mitochondrial membrane depolarization. The Golgi apparatus, probably acting as a stress sensor, intensified the conventional apoptotic mechanism induced by anthracyclines. Our data support the hypothesis that organelle-dependent initiation of cell death other than that induced by mitochondria and nucleus is a research area worthy of pursuing and suggest that the Golgi apparatus could be an ideal target for anti-cancer therapy. Of note, the activity of NLPDX in taxane-resistant DU145-R cells warrants further evaluation as second-line treatment of advanced HRPC after taxane failure.